Synthesis of some novel heterocylic compounds derived from 2-[3-(4-chlorophenyl)-5-(4-methoxybenzyl)-4H-1,2,4-triazol-4-yl]acetohydrazide and investigation of their lipase and alpha-glucosidase inhibition

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BEKİRCAN O., Ulker S., Mentese E.

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY, cilt.30, sa.6, ss.1002-1009, 2015 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 30 Sayı: 6
  • Basım Tarihi: 2015
  • Doi Numarası: 10.3109/14756366.2014.1003213
  • Dergi Adı: JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.1002-1009
  • Anahtar Kelimeler: Biheterocyclic compounds, lipase and alpha-glucosidase inhibition, Mannich bases, 1,3,4-oxadiazoles, 1,2,4-triazoles, 1,2,4-triazole-5-thiones, DERIVATIVES, ANTIBACTERIAL, ANTICANCER, TRIAZOLE, OBESITY, 1,2,4-TRIAZOLES, OXADIAZOLE, ORLISTAT
  • Karadeniz Teknik Üniversitesi Adresli: Evet

Özet

In the present study, 2-[3-(4-chlorophenyl)-5-(4-methoxybenzyl)-4H-1,2,4-triazol-4-yl]acetohydrazide (1) was used as starting compound for the synthesis of 2-{[3-(4-chlorophenyl)-5-(4-methoxybenzyl)-4H-1,2,4-triazol-4-yl]acetyl}-4-thiosemicarbazides (2a-c) and 5-{[3-(4-chlorophenyl)-5-(4-methoxybenzyl)-4H-1,2,4-triazol-4-yl]methyl}-1,3,4-oxadiazole-2-thione (5). The cyclization of compounds 2a-c in the presence of NaOH resulted in the formation of 5-{[3-( 4-chlorophenyl)-5-(4-methoxybenzyl)-4H-1,2,4-triazol-4-yl]methyl}-4-alkyl/aryl-2,4-dihydro-3H-1,2,4-triazole-3-thiones(3a-c). Aminomethylation of compounds 3a-c and 5 with formaldehyde and N-methyl/phenylpiperazine furnished Mannich bases (4a-f and 6a-b). The newly synthesized compounds were well-characterized by IR, H-1 NMR, C-13 NMR, elemental analysis and mass spectral studies. They were also screened for their lipase and alpha-glucosidase inhibition. Among the tested compound 2c (IC50 = 2.50 +/- 0.50 mu M) showed the best anti-lipase activity and compounds 2c (IC50 = 3.41 +/- 0.16 mu M) and 6a (IC50 = 4.36 +/- 0.10 mu M) showed the best anti-alpha- glucosidase activity.